Human immunodeficiency virus neutralizing antibodies and methods of use thereof

Abstract

The invention provides broadly neutralizing antibodies directed to epitopes of Human Immunodeficiency Virus, or HIV. The invention further provides compositions containing HIV antibodies used for prophylaxis, and methods for diagnosis and treatment of HIV infection.

What is claimed is: 
     
       1. A therapeutic composition comprising:
 i. A recombinantly produced monoclonal anti-HIV antibody or an HIV gp120-derived antigen-binding fragment thereof comprising the CDR1, CDR2, and CDR3 regions of the sequence of SEQ ID NO: 387 and the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 558; and 
 ii. a pharmaceutically acceptable carrier. 
 
     
     
       2. The therapeutic composition of  claim 1  wherein the anti-HIV antibody or an HIV gp120-derived antigen-binding fragment thereof neutralizes HIV virus SM53M.PB12 at an IC 50  concentration of less than 1.0 μg/mL, or an HIV virus R1166.c1 at an IC 50  concentration of less than 1.0 μg/mL, or HIV virus DU172.17 at an IC 50  concentration of less than 1.0 μg/mL. 
     
     
       3. The therapeutic composition of  claim 1  wherein the anti-HIV antibody or an HIV gp120-derived antigen-binding fragment thereof neutralizes a VRC01-resistant HIV virus at an IC 50  concentration of less than 30 μg/mL. 
     
     
       4. The composition of  claim 1 , wherein the anti-HIV antibody or antigen-binding fragment thereof comprises the sequences of SEQ ID NO: 387 and SEQ ID NO: 588. 
     
     
       5. The composition of  claim 1 , wherein the anti-HIV antibody is a full antibody. 
     
     
       6. The composition of  claim 5 , wherein the anti-HIV antibody comprises the sequences of SEQ ID NO: 387 and SEQ ID NO: 588. 
     
     
       7. A method of preventing or treating an HIV infection in a patient in need thereof comprising the steps of:
 i. identifying a patient in need of such prevention or treatment, and 
 ii. administering to said patient a therapeutically effective amount of the therapeutic composition of  claim 1 . 
 
     
     
       8. The method of  claim 7 , additionally comprising the administration of a second therapeutic agent. 
     
     
       9. The method of  claim 8 , wherein said second therapeutic agent is an antiviral agent. 
     
     
       10. A method for making an anti-HIV antibody or fragment thereof according to  claim 1 , said method comprising culturing a cell comprising a vector comprising a nucleic acid encoding the heavy and light chains of said antibody under conditions whereby the nucleic acid is expressed, and isolating said anti-HIV antibody or fragment thereof. 
     
     
       11. A method to detect the anti-HIV antibody or an antigen-binding fragment thereof of  claim 1  in a patient said method comprising isolating a biological sample from the patient and assaying the biological sample for the presence of the anti-HIV antibody or antigen-binding fragment thereof or a cell that contains at least one of the DNA or mRNA encoding the antibody or fragment. 
     
     
       12. A method for preventing or treating HIV infection or an HIV-related disease comprising steps: (a) identifying a patient in need of such prevention or treatment, (b) administering to said patient a therapeutically effective amount of at least one anti-HIV antibody, or fragment thereof, made by the method of  claim 10 . 
     
     
       13. A kit comprising
 i. at least one dose of a therapeutically effective amount of at least one anti-HIV antibody or an HIV gp120-derived antigen-binding fragment thereof according to  claim 1  and 
 ii. at least one dose of a therapeutically effective amount of an HIV agent selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an entry or fusion inhibitor, and an integrase inhibitor, 
 wherein the at least one dose of a therapeutically effective amount of at least one anti-HIV antibody or an HIV gp120-derived antigen-binding fragment thereof and the at least one dose of a therapeutically effective amount of an HIV agent can be optionally combined for simultaneous administration.